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. 1978 Dec;285:471–478. doi: 10.1113/jphysiol.1978.sp012583

Mobilization of colonic kallikrein following pelvic nerve stimulation in the atropinized cat

S Fasth *, L Hulten *, B Julienne Johnson †,‡, S Nordgren *, I J Zeitlin †
PMCID: PMC1281768  PMID: 745111

Abstract

1. Pelvic nerve stimulation (p.n.s.) in cats induces atropine-resistant colonic vasodilatation and colonic contraction. The effects of this on cat colon are mimicked by synthetic bradykinin infusions. The present study examines the effect of p.n.s. on the activation of kallikrein, the kinin-forming enzyme present in colonic tissue and its effects on the plasma kinin system in the atropinized cat.

2. Mean level (± S.D.) of mucosal kallikrein was found to be about 37 times higher in unstimulated colonic mucosa (300 ± 100 ng bradykinin equivalents min-1g-1) than in the underlying muscle (8·2 ± 6·3 ng bradykinin equiv min-1g-1).

3. After a p.n.s. of 5 min, mean kallikrein level in colonic muscle was 7·3 ± 3·5 ng bradykinin equiv min-1g-1, which was not significantly different from the control muscle kallikrein. However, there was an 86% fall in mucosal kallikrein to 41·3 ± 34·7 ng bradykinin equiv min-1g-1 after 5 min p.n.s., indicating a rapid activation and secretion of mucosal kallikrein.

4. Secretion of mucosal kallikrein was paralleled by specific depletion of plasma kininogen, the precursor of active kinin in blood draining the colon. The mean plasma kininogen level fell to 79 and 68% of the prestimulated value (3·1 ± 1·1 S.D. μg bradykinin equiv per ml. plasma) after 5 and 10 min p.n.s. respectively. Total plasma protein and haematocrit remained unaltered excluding non-specific changes due to protein extravasation or haemodilution and indicating utilization of the plasma kinin precursor.

5. Following 2 hr p.n.s., raised levels of kallikrein were detected in both colonic muscle (28 ± 2·0 bradykinin equiv min-1g-1) and mucosa 434 ± 118 ng bradykinin equiv min-1g-1). Preliminary studies using a kallikrein inhibitor indicated that the increased kallikrein levels originated from plasma.

6. Direct stimulation of the parasympathetic pelvic nerve in the atropinized cat thus produced activation of the plasma kinin system in the colon and formation of free kinins may be responsible for the mucosal vasodilatation and strong motor contraction which is not blocked by large doses of atropine. The observation that prolonged stimulation causes extravasation of plasma kallikrein, a potential inflammatory mediator, into the tissues may be of clinical significance.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AMUNDSEN E., NUSTAD K., WAALER B. A STABLE SUBSTRATE FOR THE ASSAY OF PLASMA KININ-FORMING ENZYMES. Br J Pharmacol Chemother. 1963 Dec;21:500–508. doi: 10.1111/j.1476-5381.1963.tb02018.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Amundsen E., Nustad K. Kinin-forming and destroying activities of cell homogenates. J Physiol. 1965 Aug;179(3):479–488. doi: 10.1113/jphysiol.1965.sp007674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brocklehurst W. E., Zeitlin I. J. Determination of plasmakinin & kininogen levels in man. J Physiol. 1967 Jul;191(2):417–426. doi: 10.1113/jphysiol.1967.sp008259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fasth S., Hultén L., Johnson B. J., Zeitlin I. J. Changes in the kinin system in cat colon during the atropine-resistant response to pelvic nerve stimulation [proceedings]. J Physiol. 1977 Feb;265(1):56P–57P. [PubMed] [Google Scholar]
  5. Fasth S., Hultén L. Neurohumoral regulation of motility and blood flow in the colon. Experientia. 1973 Mar 15;29(3):296–297. doi: 10.1007/BF01926486. [DOI] [PubMed] [Google Scholar]
  6. Fasth S., Hultén L. The effect of bradykinin on intestinal motility and blood flow. Acta Chir Scand. 1973;139(8):699–705. [PubMed] [Google Scholar]
  7. Fasth S., Hultén L. The effect of bradykinin on the consecutive vascular sections of the small and large intestine. Acta Chir Scand. 1973;139(8):707–715. [PubMed] [Google Scholar]
  8. Gautvik K. M., Nustad K., Vystyd J. Kininogenase activity in the stimulated submandibular salivary gland in cats. Acta Physiol Scand. 1972 Aug;85(4):438–445. doi: 10.1111/j.1748-1716.1972.tb05277.x. [DOI] [PubMed] [Google Scholar]
  9. HILTON S. M., LEWIS G. P. The relationship between glandular activity, bradykinin formation and functional vasodilatation in the submandibular salivary gland. J Physiol. 1956 Nov 28;134(2):471–483. doi: 10.1113/jphysiol.1956.sp005658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hilton S. M., Jones M. The role of plasma kinin in functional vasodilatation in the pancreas. J Physiol. 1968 Apr;195(3):521–533. doi: 10.1113/jphysiol.1968.sp008472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hultén L. Extrinsic nervous control of colonic motility and blood flow. An experimental study in the cat. Acta Physiol Scand Suppl. 1969;335:1–116. [PubMed] [Google Scholar]
  12. Seki T., Nakajima T., Erdös E. G. Colon kallikrein, its relation to the plasma enzyme. Biochem Pharmacol. 1972 May 1;21(9):1227–1235. doi: 10.1016/0006-2952(72)90284-5. [DOI] [PubMed] [Google Scholar]
  13. Zeitlin I. J. Pharmacological characterization of kinin-forming activity in rat intestinal tissue. Br J Pharmacol. 1971 Aug;42(4):648P–649P. [PMC free article] [PubMed] [Google Scholar]
  14. Zeitlin I. J., Singh Y. N., Lembeck F., Theiler M. The molecular weights of plasma and intestinal kallikreins in rats. Naunyn Schmiedebergs Arch Pharmacol. 1976 May;293(2):159–161. doi: 10.1007/BF00499221. [DOI] [PubMed] [Google Scholar]
  15. Zeitlin I. J., Smith A. N. Mobilization of tissue kallikrein in inflammatory disease of the colon. Gut. 1973 Feb;14(2):133–138. doi: 10.1136/gut.14.2.133. [DOI] [PMC free article] [PubMed] [Google Scholar]

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